The biology of cells is typically examined in cell monolayer culture applications, however, they have inherent limitations for studying the effects of and screening for drugs and predicting in vivo physiological responses (Girard et al., 2013, PLoS ONE, 8(10):e75345). As is known in the art, in vitro single cells or cell monolayer behave very differently from an in vivo organization of cells, wherein the cells are organized in a sophisticated cellular network and form tissues. In those networks, cellular responses of individual cells to drugs may be, at least to a certain extent, controlled by its extracellular environment within such network or tissue. Such extra-cellular environment, for example, includes cell-cell interaction and cell-matrix interactions. Particularly, cell-matrix interactions plays an important role in the formation of tumors and progression of tumors.
Tumor cell aggregates are believed to exhibit specific characteristic traits of their in vivo tumor counterparts. Through their more realistic demonstration of a tumor's in vivo architecture, cell-cell interactions and cell-matrix interactions, they provide more valuable information regarding the cellular differentiation, proliferation, apoptosis and gene expression of the tumor cells in question (Kim et al., 2004, Breast Cancer Research and Treatment, 85:281-291). Additionally, the use of tumor cell aggregates or tumor spheroids in drug screening assays allows one to observe the important interactions and behaviors of different cell types, and in particular, stroma cells.
For the reasons discussed above, it is particularly desirable to provide for drug validation and drug screening assays using cell aggregates or tissue fragments, which mimic more the physiological environment from where they are obtained than single cells. As such, there is a long felt need in the art to provide compositions and methods for the preparation of cell aggregates and/or tissue fragments which more accurately reflect the in vivo structure of a tissue, and more specifically, the in vivo structure of a cancerous tissue. Applicant herewith provides compositions and methods useful for the processing of tissues and for the generation of a plurality of cells, a plurality of cell aggregates and/or tissue fragments. Tissues processed according to Applicant's invention can be used in various assay systems, including, but not limited to, drug validation assays, drug screening assays, proliferation assays, metabolic assays, metastasis assays, angiogenesis assays, binding assays, biochemical assays, cellular assays, genetic assays, and the like.